Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)

NCT01934504 | Terminated Results DMC

• 2 other identifiers: DAIT ITN051AIAVATARS
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of the study is to find biological markers (certain proteins or cellular markers found in a blood test) that will inform doctors which patients diagnosed with ANCA-associated vasculitis (AAV) are most likely to be able to stop their medications suppressing their immune systems and remain in remission.

Conditions

ANCA-Associated Vasculitis

Keywords

clinical tolerance; biomarker(s) identification

Outcome Measures

Primary Outcomes (1)

• Tolerance Biomarker Identification

  Identification of biomarkers associated with clinical tolerance in patients with ANCA-associated vasculitis by comparative immunophenotyping of individual leukocyte subsets from tolerant and non-tolerant patients with AAV. Due to early study termination, data was not available to evaluate this endpoint.

  Difference from baseline to week 26

Secondary Outcomes (3)

• Tolerance Signature Stability

  Baseline to Week 26

• Tolerance Signature Versus Clinical Status

  Baseline to Week 26

• Immunosuppression Associated Signature

  Baseline to 8 Weeks Post-Immunosuppression Withdrawal

Study Arms (4)

Tolerant AAV

Tolerant participants with AAV

Procedure: Venipuncture for blood sample collection

Non-Tolerant AAV

Non-Tolerant participants with ANCA-associated vasculitis (AAV)

Procedure: Venipuncture for blood sample collection

Healthy Controls

Healthy participants that fulfill eligibility criteria -similar in age to Tolerant and Non-Tolerant AAV participants.

Procedure: Venipuncture for blood sample collection

AAV Discontinuing Immunosuppression

Participants have been in clinical remission and on minimal maintenance therapy for at least 2 years prior to screening. Their primary physicians have planned to discontinue immunosuppression medication in the next year after screening.

Procedure: Venipuncture for blood sample collection

Interventions

Venipuncture for blood sample collection PROCEDURE

Analysis samples from the blood sample collection at specific time points.

Also known as: Peripheral venous blood draw

AAV Discontinuing Immunosuppression; Healthy Controls; Non-Tolerant AAV; Tolerant AAV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Non-tolerant: Patients who have persistently active disease. Tolerant: Those patients who have become ANCA negative, having been ANCA positive at the time of their acute presentation but have been in prolonged disease- free remission off all immunotherapy for at least two years. Healthy controls: Individuals with similar age distribution to participants in the Non-tolerant and Tolerant cohorts.

You may qualify if:

• Tolerant AAV participants:
• Age 18 years or older
• Diagnosis of granulomatosis with polyangiitis (Wegener's, GPA) or microscopic polyangiitis (MPA) according to the definitions of the Chapel Hill Consensus Conference (CHCC)
• History of being myeloperoxidase (MPO)-ANCA positive during a disease flare
• In clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) = 0 and off all immunosuppression for ≥ 2 years
• Negative MPO-ANCA and proteinase 3 (PR3)-ANCA by ELISA at screening
• For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening
• Ability to sign and understand informed consent
• Willingness to comply with study procedures.
• Non-Tolerant AAV participants:
• Age 18 years or older
• Diagnosis of granulomatosis with polyangiitis (Wegener's), GPA or microscopic polyangiitis (MPA) according to the definitions of the CHCC
• History of being MPO-ANCA positive during a disease flare
• Within the past 5 years, must have had a disease exacerbation, defined as an increase in the BVAS/WG score and re-institution of immunosuppressive therapy after therapy had been reduced or completely discontinued
• In clinical remission with BVAS/WG = 0 and on minimal maintenance therapy for ≥3 months prior to the screening visit. Minimal maintenance therapy is defined as:

You may not qualify if:

• Tolerant AAV Participants:
• Use of systemic intravenous (IV) or oral glucocorticoids for ˃ 1 month for any non-vasculitis indication within 8 weeks of the screening visit
• Any prior treatment with rituximab
• Presence of known chronic viral infections or autoimmune diseases
• History of malignancy, excluding non-melanomatous skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.
• Non-Tolerant AAV participants:
• Use of IV pulse glucocorticoids (methylprednisolone or other) or cyclophosphamide within the year prior to the screening visit
• Use of IV or oral glucocorticoids for \> 1 month for any non- vasculitis indication within 8 weeks of screening visit
• Any prior treatment with rituximab
• Maintenance therapy with methotrexate within 3 months of the screening visit
• Presence of known chronic viral infections or other autoimmune diseases
• History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.
• Healthy Controls:
• Use of IV or oral glucocorticoids for \> 1 month for any non-vasculitis indication within 8 weeks of the screening visit
• Presence of known chronic viral infections or other autoimmune diseases

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (3)

Addenbrooke's Hospital

Cambridge, England, CB2 0QQ, United Kingdom

Location

University College London, Centre for Nephrology

London, England, NW32PF, United Kingdom

Location

Hammersmith Hospital

London, England, W12 0HS, United Kingdom

Location

Related Links

• The National Institute of Allergy and Infectious Diseases
• Immune Tolerance Network (ITN)

Biospecimen

Retention: SAMPLES WITH DNA

* peripheral blood mononuclear cells (PBMCs) * whole blood RNA * serum

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

Study termination due to slow enrollment, resulting in no outcome analyses.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Alan Salama, MD

  University College London, Centre for Nephrology

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2013
• First Posted: September 4, 2013
• Study Start: December 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: May 20, 2016
• Results First Posted: May 20, 2016

Record last verified: 2016-04

Locations

GB (3)